1. Field of the Invention
This invention relates to a process and compounds useful for the preparation of methanesulfonamides. In particular, it relates to a process and compounds useful for the preparation of (S)-(−)-N[-4[ethyl(6-fluoro-6-methyl-heptyl) amino]-1-hydroxybutyl]phenyl] methanesulfonamide hemifumarate salt. This saltis disclosed in U.S. Pat. No. 5,405,997 as a Class III antiarrhythmic compound which selectively prolongs the action potential duration and concomitantly increases the refractory period of heart cells without significant effects on cardiac condition. The essential parts of U.S. Pat. No. 5,405,997 are herein incorporated by reference.
2. Prior Art
The process described for preparing (S)-(−)-N-[4-[4-ethyl(6-flouro-6-methyl-heptyl) amino-1-hydroxybutyl]phenyl]methanesulfonamide hemifumarate salt in U.S. Pat. No. 5,405,997 involved introduction of the fluoroamine moiety early in the synthesis. This results in the formation of a commercially unacceptable number of impurities.
The use of sodium triacetoxy borohydride for reductive amination of utilizing 1,2-dichloroethane, tetrahydrofuran or acetonitrile as solvents is described in Abdel-Magid, A.F. et al, J. Org. Chem. 1996, 61, 3849-3862.
The direct conversion of a hydroxy ester to a lactone employing basic conditions with no loss in chiral purity was reported by Corey. E.J. et al, J. Am. Chem. Soc. 1987, 109, 7926-7927. However, when subjected to the same basic conditions, hydroxy ester IIc of this invention resulted in a lactone that was racemic.
The use of the enzyme porcine pancreatic lipase to convert hydroxy ester to lactones is also known, Gutman, A. L. et al, J. Org. Chem., 1990, 55, 3546-3552. The conversion of hydroxy acids to lactones under acidic conditions is described by Thompson, A. L. et al, Tetrahedron Lett. 1990, 31, 6953-6956. When the hydroxy ester of this invention is subjected to the ester hydrolysis of Thompson et al, a complex mixture is obtained.
Lactonization of hydroxy esters under acidic conditions has also been reported by Sibi, M. et al, Tetrahedron Let 1992, 5681-5684. Williams et al, Tetrahedron Let, 1989, 1331-1334 and Mohr, P. et al, Helv. Chim. Acta 1987, 142-152.
The complex interaction of physical properties that define the capacity of a compound for upgrading (resolution) was described by Jacques, J. et al, “Enantiomers Racemates and Resolutions”, John Wiley & Sons, New York, 1981.